The predictive value of the oncogene product ErbB-2 for chemosensitivity of tumors is still unclear. We therefore correlated the in vitro chemosensitivity of breast cancer specimens from 125 patients with the respective expression levels of ErbB-2. Twenty-six percent of the patients were premenopausal. Chemosensitivity was tested with the adenosine triphosphate cell viability assay and ErbB-2 content was assessed in the same specimens by ELISA. With the cut-off value used 34% of the patients had tumors with positive ErbB-2 levels. The mean ErbB-2 amount of positive tumors was 388 U/mg +/- 254 and of negative tumors 65 U/mg +/- 36. The mean survival fractions (SF) in the chemosensitivity assay at 0.25 peak plasma concentration (PPC) of a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were not significantly different for ErbB-2-positive and for ErbB-2-negative tumors (0.68 and 0.65, respectively (p = 0.6)). The median SF for positive tumors was 0.68 and for negative tumors 0.62, respectively. Similarly, at four times the PPC of CMF no significant differences in SF of ErbB-2-positive and -negative specimens were found (p = 0.8). Comparison of the median of ErbB-2-protein content of CMF-sensitive tumors with that of CMF-resistant tumors also yielded no significant difference. Taken together, no significant association between in vitro CMF-chemosensitivity and expression levels of ErbB-2 in tumors of patients with primary chemotherapy naive breast cancer could be determined.